Colorectal cancer susceptibility loci and influence on survival

Genes Chromosomes Cancer. 2018 Dec;57(12):630-637. doi: 10.1002/gcc.22674. Epub 2018 Oct 22.


Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. To evaluate the potential influence of colorectal cancer susceptibility SNPs on disease prognosis, we investigated whether GWAS-identified colorectal cancer risk SNPs and polygenic risk scores (PRSs) might be associated with survival among colorectal cancer patients. A total of 1374 colorectal cancer patients were recruited from the Korean National Cancer Center. For genotyping, 30 colorectal cancer-susceptibility SNPs previously identified by GWAS were selected. The Cox proportional hazard model was used to evaluate associations of these risk SNPs and PRSs with disease-free survival (DFS) and overall survival (OS). The prognostic values were compared between genetic and nongenetic models using Harrell's c index. During the follow-up period (median: 88, 91 months for DFS and OS), 570 DFS (41.5%) and 487 OS (35.4%) events were observed. We found that 5 SNPs were significantly associated with DFS or OS among colorectal cancer patients at P < .05: rs10936599 at 3q26.2 (MYNN), rs704017 at 10q22.3 (ZMIZ1-AS1), rs11196172 at 10q25.2 (TCF7L2), rs3802842 at 11q23.1 (COLCA1-2), and rs9929218 at 16q22.1 (CDH1). The PRSs constructed using these 5 SNPs were associated with worse survival (DFS: Ptrend = .02 unweighted PRS, Ptrend = .01 weighted PRS, OS: Ptrend = 3.7 × 10-3 unweighted, Ptrend = .02 weighted PRS). Our results suggest that several colorectal cancer susceptibility SNPs might also be related to survival by influencing disease progression.

Keywords: colorectal cancer; genetic epidemiology; polygenic risk score; single-nucleotide polymorphism; survival analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / physiopathology
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Proportional Hazards Models
  • Risk Assessment
  • Survival Analysis*